Amino Acids and Peptides: Structure, Properties, and Bonding

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5.1 Amino Acids

The Structure of an α-Amino Acid

Amino acids are the building blocks of proteins, each containing a central α-carbon atom bonded to four distinct groups: an amino group, a carboxylic acid group, a hydrogen atom, and a unique side chain (R group).

α-Carbon: The central carbon atom to which all groups are attached.
Asymmetry: When the R group is not hydrogen, the α-carbon is a chiral center (asymmetric carbon).
Zwitterion: At neutral pH, the amino group is protonated (–NH3+) and the carboxylic acid group is deprotonated (–COO–), resulting in a molecule with both positive and negative charges.
General Structure:

Example: Glycine is the simplest amino acid, with R = H.

α-Amino Acid Stereochemistry

The spatial arrangement of atoms around the α-carbon gives rise to stereoisomerism in amino acids.

Chirality: Most amino acids (except glycine) are chiral, meaning they have non-superimposable mirror images.
Enantiomers: The two mirror-image forms are called L- and D- isomers. Proteins are composed almost exclusively of L-amino acids.
Fischer Projection: A two-dimensional representation used to depict stereochemistry.

Example: L-alanine and D-alanine are enantiomers; L-alanine is the form found in proteins.

Classification of Naturally Occurring Amino Acids

The 20 standard amino acids are classified based on the properties of their side chains (R groups).

Nonpolar Aliphatic: Glycine, Alanine, Valine, Leucine, Isoleucine, Proline, Methionine
Aromatic: Phenylalanine, Tyrosine, Tryptophan
Polar Uncharged: Serine, Threonine, Cysteine, Asparagine, Glutamine
Positively Charged (Basic): Lysine, Arginine, Histidine
Negatively Charged (Acidic): Aspartic acid, Glutamic acid

Example: Tyrosine and tryptophan are aromatic amino acids that absorb UV light.

General Properties of Amino Acids

Amino acids have unique chemical and physical properties that influence protein structure and function.

UV Absorption: Aromatic amino acids (tyrosine, tryptophan) absorb UV light at 280 nm, which is used to quantify protein concentration. Nucleic acids absorb most strongly at 260 nm.
Ionization: Amino acids contain ionizable groups with characteristic pKa values.

Group Type	Typical pKa Range
α-Carboxyl	3.5–4.0
Side-chain carboxyl (Asp, Glu)	4.0–4.8
Imidazole (His)	6.5–7.4
Cysteine (–SH)	8.0–9.0
Phenolic (Tyr)	9.5–10.5
α-Amino	8.0–9.0
Side-chain amino (Lys)	9.8–10.4
Guanidinium (Arg)	~12

Titration Curves and Isoelectric Point (pI)

Titration Curve: Shows how the charge on an amino acid changes with pH.
pI (Isoelectric Point): The pH at which the net charge of the molecule is zero.

Example: Histidine's titration curve demonstrates three ionizable groups, with the pI corresponding to the point where the net charge is zero.

Posttranslational Modification of Amino Acids

After translation, amino acids in proteins can be chemically modified, affecting protein function and regulation.

Functions: Signaling pathways, calcium binding, stabilizing structures (e.g., collagen), gene expression or suppression.
Examples: Phosphoserine, 4-hydroxyproline, N-acetyllysine, γ-carboxyglutamate.

5.2 Peptides and the Peptide Bond

Peptide Bond Formation between Amino Acids

Peptide bonds link amino acids together to form peptides and proteins.

Condensation Reaction: The amino group of one amino acid reacts with the carboxyl group of another, releasing water and forming a peptide bond.
Energetics: This reaction is not thermodynamically favorable and is coupled to ATP hydrolysis during protein biosynthesis.

Equation:

Structure of the Peptide Bond

The peptide bond has unique structural properties due to electron delocalization.

Planarity: The peptide bond is planar and rigid due to resonance between the carbonyl and amide nitrogen.
Stability: This planarity contributes to the stability of protein structures.

Peptide Bond Cleavage

Peptide bonds can be hydrolyzed, breaking the chain into smaller peptides or amino acids.

Hydrolysis: The standard free energy change () for peptide bond hydrolysis is about –10 kJ/mol.
Stability: Peptides are stable unless exposed to strong acid at high temperature or a catalyst (protease).
Proteases: Enzymes that catalyze the cleavage of specific peptide bonds.

Sequence Specificities for Proteases

Different proteases cleave peptide bonds at specific amino acid sequences.

Enzyme	Preferred Site	Source
Trypsin	R, K (Arg, Lys)	Digestive systems of animals
Chymotrypsin	F, Y, W (Phe, Tyr, Trp)	Digestive systems of animals
Thrombin	R (Arg)	Blood (clotting)
V8 protease	E (Glu)	Staphylococcus aureus
Cyanogen bromide	M (Met)	Chemical reagent
Additional info:	Other proteases have unique specificities.

Oligopeptides and Polypeptides

Peptides are classified by the number of amino acid residues they contain.

Oligopeptides: Chains of 3–15 amino acids.
Polypeptides: Chains containing more than 15 amino acids.

Example: A tetrapeptide contains four amino acid residues.

Important Peptide Regions

Peptides and proteins have distinct regions that determine their structure and function.

N-terminus: The end with a free amino group.
C-terminus: The end with a free carboxyl group.
Main Chain (Backbone): The repeating sequence of atoms common to all peptides.
Side Chains: The variable R groups that project from the main chain.

Common Modifications of Amino- and Carboxy-Termini in Peptides

The N- and C-termini of peptides can be chemically modified, affecting stability and function.

N-formyl group (blocks N-terminus)
N-acetyl group (blocks N-terminus)
C-terminal amide (blocks C-terminus)

Peptides and Proteins as Polyampholytes

Peptides and proteins can act as polyampholytes, molecules with multiple ionizable groups that can carry both positive and negative charges depending on pH.

Charge Variation: As pH increases, the overall charge becomes more negative; as pH decreases, it becomes more positive.
Biological Relevance: The charge state affects protein solubility, structure, and interactions.